Recruiting
Phase 1
Phase 2

AVB-101

Sponsor:

AviadoBio Ltd

Code:

NCT06064890

Conditions

Frontotemporal Dementia

FTD

FTD-GRN

Dementia, Frontotemporal

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Not accepted

Interventions

Intrathalamic AAV.PGRN administration

Intrathalamic AVB-101

Study Details

Brief summary:

The goal of this clinical study is to learn about an investigational gene therapy product called AVB-101, which is designed to treat a disease called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). FTD-GRN is an early-onset form of dementia, a progressive brain disorder that affects behavior, language and movement. These symptoms result from below normal levels of a protein called progranulin (PGRN) in the brain, which leads to the death of nerve cells (neurons), affecting the brain's ability to function.

The main questions that the study aims to answer are:

1. Is a one-time treatment with AVB-101 safe for patients with FTD-GRN?
2. Does a one-time treatment with AVB-101 restore PGRN levels to at least normal levels?
3. Could AVB-101 work as a treatment to slow down or stop progression of FTD-GRN?

In this study there is no placebo (a dummy pill or treatment used for comparison purposes), so all participants will receive a one-time treatment of AVB-101 delivered directly to the brain, with follow-up assessments for 5 years.

Conditions

Frontotemporal Dementia

FTD

FTD-GRN

Dementia, Frontotemporal

Study ID

NCT06064890

Start date

Aug 30, 2023

Status verified date

Jul, 2026

Completion date

Mar 21, 2030

Anticipated

Primary completion date

Apr 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Male or female, 30 to 75 years of age
  • Carriers of a pathogenic GRN mutation
  • FTD as evidenced by CDR + NACC FTLD global score of 0.5, 1.0, or 2.0
  • Presence of 1 or more of the criteria for diagnosis of possible bvFTD or PPA
  • Able and willing to comply with all procedures and the study visit schedule
  • Able and willing to give written informed consent prior to study participation, and agree to designate a legal representative to act on their wishes to continue participation should they lose capacity to consent at some point during the study OR If, in the Investigator's opinion, the subject lacks capacity to consent, written informed consent of their legal representative must be obtained in accordance with local laws, regulations, and/or customs. In countries where local laws, regulations, and/or customs do not permit subjects who lack capacity to consent to participate in this study, these subjects will not be enrolled
  • An identified, informed study partner who is able and willing to support the participant in the study and to provide assessments of the participant during the study

Exclusion Criteria:

  • Severe dementia, defined as CDR + NACC FTLD global score of 3.0, or other symptoms that preclude the ability to comply with study procedures and/or pose unacceptable safety risk to the subject
  • Any concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency
  • Clinically significant abnormality on MRI at Screening considered to be a contraindication to Intrathalamic infusion
  • Surgically significant pattern of brain atrophy on MRI at Screening that interferes with planned neurosurgical trajectory
  • Previous treatment with any gene or cell therapy
  • Previous treatment with any investigational medicinal product (IMP) within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment
  • Concomitant disease, any clinically significant laboratory abnormality, or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the participant or interfere with study conduct or the participant's ability to comply with study procedures including neurosurgical administration under anesthesia

Study Design

Enrollment

18 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1 (dose 1)

Initial dose

experimental: Cohort 2 (dose 2)

Escalated dose

experimental: Cohort 3 (dose 3)

Additional dose

experimental: Cohort 4 (dose 4)

Additional dose

Interventions

Intrathalamic AAV.PGRN administration

One-time MRI-guided stereotaxic infusion of AAV.PGRN into the brain

Intrathalamic AVB-101

AVB-101 is made from an adeno-associated virus, serotype 9 (AAV9). AAVs are small viruses that are naturally occurring and do not cause illness or infection on their own. AVB-101 has been modified to contain a copy of the correct (non-mutated) GRN gene, plus some other genetic material to enable the GRN gene to function inside neurons (cells within the brain). AVB-101 has also been modified so that it cannot divide and make new copies of itself (known as 'replication'), which means that it cannot cause disease or a large immune response in your body.

Primary outcome measure

  • Number and incidence of AEs and SAEs [ Time Frame: Up to week 26 ]
  • Change from baseline in the Mini-Mental State Examination (MMSE) [ Time Frame: Up to week 12 ]
  • Incidence of treatment emergent suicidal ideation or behavior [ Time Frame: 26 week initial, 5-year total follow-up period ]
  • Incidence of treatment-emergent clinically significant abnormalities in clinical examination findings [ Time Frame: 5-year total follow-up period ]
  • Incidence of treatment-emergent clinically significant abnormalities in safety laboratory values [ Time Frame: 5-year total follow-up period ]
  • Change from baseline in brain structure [ Time Frame: 5-year total follow-up period ]

Central Contacts and Locations

Central contacts

AviadoBio Clinical Trials

+44 203-089-7917clinicaltrials@aviadobio.com

Locations

The Ohio State University (OSU) Wexner Medical Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Jennifer Icenhour

614-293-6882jennifer.icenhour@osumc.edu

Andrea Davis

614-688-6412andrea.davis@osumc.edu

Vanderbilt University Medical Centre

Recruiting

Nashville, Tennessee, United States, 37232

Houston Methodist Hospital

Recruiting

Houston, Texas, United States, 77030

Contacts

Manuel Navarro

346-238-1564mnavarro2@houstonmethodist.org

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada

Contacts

Sabrina Armstrong

(416) 480-6100sabrina.armstrong@sri.utoronto.ca

More Information

Sponsor

AviadoBio Ltd

Last update posted

Aug 13, 2026

Last verified

Jul, 2026

Keywords

  • Gene Therapy
  • AAV
  • Intrathalamic
  • Intraparenchymal
  • Progranulin
  • Behavioral Variant FTD
  • Primary Progressive Aphasia
  • PGRN
  • Granulin
  • Dementia
  • Dementia Gene Therapy
  • AAV9

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by AviadoBio Ltd on 2026-08-13.